(Inside Science) – An interview with Steven Kalkanis at the Henry Ford Health System.
What does the future of brain cancer treatment look like?
“You know, there has never been a more hopeful time as an era, as a field, in terms of what we have in our armamentarium to treat brain tumors. We have the molecular genetic codes that we're breaking on a daily basis to try and figure out why some patients with brain tumors respond very well to one therapy versus another patient with seemingly the same diagnosis [who] may not respond at all. Now we have an ability to test the genetics of each patient's tumor to develop a targeted treatment therapy for them.
“At the same time, we've had so many advances in imaging, so that we have the advantage now of being able to take intraoperative MRI scans, and fluorescent technology to make tumors light up in the operating room. We can track where they are, and it makes surgery safer. It allows surgeons to take out more of the tumor, which then leaves to a better prognosis for our patients. But then it doesn't stop there. Once we get the tissue, we can then analyze it based on that particular patient's, and that particular tumor's, genetic profile to develop a treatment plan that is unique only for that patient.
“And that has moved the needle more than anything else I think in the last half century. And so, as dreaded of a problem as this is, I think there's never been a more hopeful time for what we're able to offer patients.”
What is the cancer moonshot?
“So, the cancer moonshot is a wonderful motivation and impetus to get all researchers from around the globe focused on removing all types of barriers to advancement. I was very honored to represent Henry Ford at the White House with former Vice President Biden when he launched this, and specifically for brain tumors, the power of the moonshot is thinking about cancer treatment in a global crowdsourcing way.
“If a patient in Beijing or London or Argentina or Chicago or Los Angeles has a tumor, that genetic profile can be uploaded, and it's a real-time iteration so that the next patient that has that same profile will have the benefit of the experience of all of those patients that had a similar phenotype or genotype from around the world. And we will know if one drug that worked for one patient with that profile is appropriate to give to the next one. And all this does is basically take 10 or 20 years of research and hopefully compress it into a few years so that we have a better chance to find a cure, or at least a real advance in treatment much sooner than we otherwise would.
“So, I think the moonshot is meant to really share information and make data more accessible, so that practitioners and researchers around the world can collaborate better and get to an answer more quickly.”
Brain Cancer: Evolving Standard of Care
What is the current standard of care for brain cancer treatment?
“Our current standard of care is to take out as much of the tumor as is safe, and we do this through a variety of imaging techniques and surgical techniques. But that's not enough. There are microscopic cells that are left behind that have sort of fingerlike projections in the brain. So we need something else besides the surgery to make sure that these tumors don't recur. And so, the standard right now is to do surgery. And then that's followed by a pretty aggressive regimen of radiation therapy and chemotherapy.
“And right now, we have some basic drugs that have been around for a while that are given to all patients that have a certain type of malignant brain tumor. The wonderful, hopeful advance is that we have the ability to understand that newer drugs might be more effective for these patients, or perhaps an injection of a virus that starts dividing and selectively kills these cancer cells, or a whole other upregulating of the immune pathway so that the body's own immune system can be recruited to fight cancer along with these agents.
“We can put all of this together now to come up with a personalized treatment plan. And so we very quickly are moving from that standard of care to really a personalized, customized approach for each individual patient.”
New Tools for Treating Cancer of the Brain
What is laser interstitial thermal therapy?
“One of the other incredible tools at our disposal is something called LITT, laser interstitial thermal therapy, or laser ablation. And it's essentially the ability to heat up, in a very specific way, tumors or lesions, or even a focus of seizures for epilepsy inside the brain. So, you can really heat up and kill cells that are part of a tumor, but even a cell layer away, it doesn't affect the normal brain.
“We do this in an MRI scan so that we can tell the temperature of the surrounding tissue, and we can identify the path of this laser probe that we insert directly into the center of the tumor. And this has been a tremendous way of treating smaller lesions that might be very deep in the brain or in a region where we can't readily get to through traditional surgical means. And it just adds to our ability to treat these lesions.”
What is 5-ALA and how does it help brain surgeries?
“It's a very innovative technology where patients right in the morning of surgery drink a substance that looks like elastic milk, and it gets absorbed. And using a protoporphyrin pathway that happens in all of us through normal mechanisms, this substance gets converted into something that is fluorescent. So, if you shine a certain light on it, tumor cells that have this substance taken up in it shine this very bright violet-magenta color.
“And the interesting thing is only tumor cells have the ability to have this 5-ALA conversion happening, which means that you could have a tumor cell right next to an individual normal brain cell, and only the tumor cell would light up. And this has tremendous advantages for surgeons to be able to identify these very tiny projections that are hard to see even under a microscope. And surgery's dangerous. It's the brain, and it's intermixed with normal tissue.
“And so, to be able to give surgeons the opportunity to have a pathway and a trajectory where you're only targeting the malignant cells, that's a huge advantage.”
What is 5-ALA like in the operating room?
“It was a very dramatic thing. The very first case I ever did with 5-ALA, I thought that I was done with the surgery. I had removed all of it that I could see. I even took an extra little bit to make sure that the margins were clear. And we then turned on the microscope light. And lo and behold, there was a little area of pinkish-magenta color that was peeking through. And I did a little bit more resection and found an entirely separate little nub of tumor tissue that otherwise would have been missed.”